Atsushi Sugiyama1, Keith G. Lurie2, Simon M.N.
Efange3, Akira Takahara1,
Shunji Takehana1 and Keitaro Hashimoto1
1Departmentﾊof Pharmacology, Yamanashi Medical University,
Tamaho-cho, Nakakoma-gun, Yamanashi 409-3898, Japan
2CardiacﾊArrhythmia Center, Department of Medicine and 3Departmentﾊof
Radiology,
University of Minnesota, Minneapolis, MN 55455, USA
Abstract: m-(Iodobenzyl)trozamicol (MIBT) is a recently
discovered vesamicol analogue. It has been shown that radiolabelled [125I]MIBT
can be used as a marker of cholinergic innervation in the heart as well
as in the brain. The purpose of this study was to analyze the direct effects
of MIBT on the atrioventricular and intraventricular conduction in addition
to the coronary blood flow using the canine isolated, blood-perfused atrioventricular
node preparation. Intracoronary administration of MIBT suppressed the atrioventricular
and intraventricular conduction, while it increased the coronary blood flow.
The effect and duration of action on the intraventricular conduction was
less pronounced compared with other effects. Moreover, the doses of MIBT
needed to cause negative dromotropic and coronary vasodilator effects in
this study was much greater than those needed for imaging the cardiac cholinergic
innervation. Pretreatment of the preparations with a muscarinic receptor
antagonist, atropine, did not block these effects of MIBT, suggesting that
MIBT may possess muscarinic receptor-independent ion channel activity in
the cardiac conduction system and coronary arteries.
Keywords: m-(Iodobenzyl)trozamicol (MIBT), Vesamicol, AV node,
Conduction, Coronary blood flow